title: Donor-specific HLA alloantibodies: long-term impact on cardiac allograft vasculopathy and mortality after heart transplant.
abstract: OBJECTIVE
  The clinical significance of anti-HLA-alloantibodies remains controversial. Recent studies have linked development of donor-specific HLA-antibodies to chronic allograft rejection and graft loss after heart, kidney, and lung transplants. We investigated the clinical impact of donor-specific humoral alloreactivity during the follow-up of heart transplant recipients.
  
  
  METHODS
  The sera of 213 heart transplant recipients were screened by enzyme-linked immunosorbent assay for HLA-antibody production. The antigen specificity of the detected HLA class I and class II antibodies was identified using a Luminex assay. Outcome variables were survival, cardiac allograft vasculopathy, and cellular rejection.
  
  
  RESULTS
  The cumulative incidence of alloantibody formation was 23/213 patients (10.8%). The majority of detected alloantibodies were donor-specific for HLA class II. Mean follow-up at antibody measurements was 7 -/+ 4.9 years. Freedom from vasculopathy at 5 and 10 years was 77.9% and 26% in donor-specific HLA-antibody-positive patients compared with 84.6% and 65.2% in antibody-negative controls (P = .025). Freedom from treated, biopsy-proven rejection was 44.4% for donor-specific HLA-antibody-positive patients compared with 70.2% in the controls (P = .06). Multivariate analyses identified donor-specific HLA antibody positivity as an independent risk factor for vasculopathy.
  
  
  CONCLUSIONS
  Our results demonstrate a strong correlation between the development of donor-specific HLA antibodies and adverse outcomes after heart transplant. Detection of donor-specific HLA antibodies might identify high-risk patients and offer an opportunity for early clinical intervention and modification of immunosuppression.
authors.affiliation: Department of Cardiac Surgery, University Hospital Grosshadern, Ludwig-Maximilians-University, Marchioninistrasse 15, 81377 Munich, Germany. Ingo.Kaczmarek@med.uni-muenchen.de
authors.forename: Ingo
authors.initials: I
authors.lastname: Kaczmarek
authors.forename: Marcus-Andre
authors.initials: MA
authors.lastname: Deutsch
authors.forename: Teresa
authors.initials: T
authors.lastname: Kauke
authors.forename: Andres
authors.initials: A
authors.lastname: Beiras-Fernandez
authors.forename: Michael
authors.initials: M
authors.lastname: Schmoeckel
authors.forename: Calin
authors.initials: C
authors.lastname: Vicol
authors.forename: Ralf
authors.initials: R
authors.lastname: Sodian
authors.forename: Bruno
authors.initials: B
authors.lastname: Reichart
authors.forename: Michael
authors.initials: M
authors.lastname: Spannagl
authors.forename: Peter
authors.initials: P
authors.lastname: Ueberfuhr
mesh_terms: D000328:Adult; D000917:Antibody Formation; D002311:Cardiomyopathy, Dilated / Q000601:surgery; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000453:epidemiology / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology* / Q000401:mortality; D006801:Humans; D007518:Isoantibodies / Q000097:blood*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016019:Survival Analysis; D017741:Survivors; D013997:Time Factors; D014019:Tissue Donors
chemical_list: D006680:HLA Antigens; D007518:Isoantibodies